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| 1 | 帕博利珠单抗单用或与放疗联用治疗转移性非小细胞肺癌:两个随机试验的汇总分析显示文摘背景放疗可以提高整个机体对免疫治疗的应答。在Ⅱ期PEMBRO-RT研究和Ⅰ/Ⅱ期MDACC研究中,患有转移性非小细胞肺癌(NSCLC)的患者被随机分配入组,接受免疫治疗(帕博利珠单抗)+放疗联合疗法,或免疫治疗单一疗法。当上述2个研究单独分析时,联合疗法组显示出潜在获益。由于每个研究的样本量较小,缓解率和结局并未显示出统计学意义,然而却有显著的临床获益。因此,本研究进行汇总分析,来判断放疗是否会改善转移性NSCLC患者的免疫治疗应答。方法PEMBRO-RT和MDACC研究纳入标准:患者年龄≥18岁,患有转移性NSCLC,且有≥1处未经放疗照射的病灶,以便进行射野外应答监测。PEMBRO-RT研究纳入曾接受过化疗患者,MDACC研究纳入曾接受过治疗或新诊断患者。2个研究中的患者均未接受过免疫治疗。在PEMBRO-RT研究中患者被等比例随机分配入组,并根据吸烟状态进行分层(分为<10年组和≥10年组)。MDACC研究的患者根据放疗计划可行性被等比例随机分配入2个受试组。由于联合治疗组的干预本质,每个研究中的放疗均不适用盲法。在2个研究中,不论是否进行放疗,均静脉滴入帕博利珠单抗(每3周200 mg)。在PEMBRO-RT研究中,在放疗(24 Gy 3次分割照射)结束后1周给予第1剂帕博利珠单抗。在MDACC研究中,在第1次放疗(50 Gy 4次分割照射或45 Gy 15次分割照射)同时给予帕博利珠单抗。仅检测未经照射病灶的应答。本研究的终点为最佳射野外(远隔)应答率(ARR)、最佳射野外疾病控制率(ACR)、12周时ARR、12周时ACR、无进展生存期(PFS)和总生存期(OS)。2个研究的意向治疗(ITT)人群均纳入分析。PEMBRO-RT研究(NCT02492568)和MDACC研究(NCT02444741)均在ClinicalTrials.gov上注册。发现纳入148例患者,76例接受帕博利珠单抗治疗,72例接受帕博利珠单抗+放疗治疗。所有患者随访时间中位数为33个月[四分位距(IQR):32.4~33.6]。148例患者中124例(84%)组织学特征为非鳞癌,111例(75%)患者曾经接受过化疗。组间没有基线特征差异,包括PD-L1表达状态和转移灶体积。最常见的照射部位为肺转移灶(39%,28/72)、胸腔内淋巴结(21%,15/72)和非原发灶(17%,12/72)。帕博利珠单抗组和联合治疗组的最佳ARR分别为19.7%(15/76)和41.7%(30/72),OR=2.96,95%CI:1.42~6.20,P=0.0039;最佳ACR分别为43.4%(33/76)和65.3%(47/72),OR=2.51,95%CI:1.28~4.91,P=0.0071;PFS中位数分别为4.4(IQR:2.9~5.9)和9.0个月(IQR:6.8~11.2),HR=0.67,95%CI:0.45~0.99,P=0.045;OS中位数分别为8.7(IQR:6.4~11.0)和19.2个月(IQR:14.6~23.8),OR=0.67,95%CI:0.54~0.84,P=0.0004。在汇总分析中没有发现新的安全问题。解读帕博利珠单抗免疫疗法+放疗显著提高转移性NSCLC患者的应答和改善治疗结局。这些结果需要在三期临床试验中进行验证。 | 陈大卫(翻译) 于金明(校对) Willemijn S M E Theelen Vivek Verma Brian P Hobbs Heike M U Peulen Joachim G J V Aerts Idris Bahce Anna Larissa N Niemeijer Joe Y Chang Patricia M de Groot Quynh-Nhu Nguyen Nathan I Comeaux George R Simon Ferdinandos Skoulidis Steven H Lin Kewen He Roshal Patel John Heymach Paul Baas James W Welsh | 2021 | 中华肿瘤防治杂志2021，28，24： | 49 |
| 2 | Total knee arthroplasty and fractures of the tibial plateau显示文摘Tibial plateau fractures are common injuries that occur in a bimodal age distribution. While there are various treatment options for displaced tibial plateau fractures, the standard of care is open reduction and internal fixation(ORIF). In physiologically young patients with higher demand and better bone quality, ORIF is the preferred method of treating these fractures. However, future total knee arthroplasty(TKA) is a consideration in these patients as post-traumatic osteoarthritis is a common long-term complication of tibial plateau fractures. In older, lower demand patients, ORIF is potentially less favorable for a variety of reasons, namely fixation failure and the need for delayed weight bearing. In some of these patients, TKA can be considered as primary mode of treatment. This paper will review the literature surrounding TKA as both primary treatment and as a salvage measure in patients with fractures of the tibial plateau. The outcomes, complications, techniques and surgical challenges are also discussed. | Kenneth A Softness Ryan S Murray Brian G Evans | 2017 | World Journal of Orthopedics2017，8，2： | 15 |
| 3 | Maintenance infliximab for Crohn’s disease: the ACCENT I randomised trial显示文摘 | Stephen B Hanauer Brian G Feagan Gary R Lichtenstein Lloyd F Mayer S Schreiber Jean Frederic Colombel Daniel Rachmilewitz Douglas C Wolf Allan Olson Weihang Bao Paul Rutgeerts | 2002 | The Lancet2002，，9317： | 6 |
| 4 | Model combining pre-transplant tumor biomarkers and tumor size shows more utility in predicting hepatocellular carcinoma recurrence and survival than the BALAD models显示文摘AIM To assess the performance of BALAD, BALAD-2 and their component biomarkers in predicting outcome of hepatocellular carcinoma(HCC) patients after liver transplant.METHODS BALAD score and BALAD-2 class are derived from bilirubin, albumin, alpha-fetoprotein(AFP), Lens culinaris agglutinin-reactive AFP(AFP-L3), and des-gammacarboxyprothrombin(DCP). Pre-transplant AFP, AFP-L3 and DCP were measured in 113 patients transplanted for HCC from 2000 to 2008. Hazard ratios(HR) for recurrence and death were calculated. Univariate and multivariate regression analyses were conducted. C-statistics were used to compare biomarker-based to predictive models. RESULTS During a median follow-up of 12.2 years, 38 patients recurred and 87 died. The HRs for recurrence in patients with elevated AFP, AFP-L3, and DCP defined by BALAD cut-off values were 2.42(1.18-5.00), 1.86(0.98-3.52), and 2.83(1.42-5.61), respectively. For BALAD, the HRs for recurrence and death per unit increased score were 1.48(1.15-1.91) and 1.59(1.28-1.97). For BALAD-2, the HRs for recurrence and death per unit increased class were 1.45(1.06-1.98) and 1.38(1.09-1.76). For recurrence prediction, the combination of three biomarkers had the highest c-statistic of 0.66 vs. 0.64, 0.61, 0.53, and 0.53 for BALAD, BALAD-2, Milan, and UCSF, respectively. Similarly, for death prediction, the combination of three biomarkers had the highest c-statistic of 0.66 vs 0.65,0.61, 0.52, and 0.50 for BALAD, BALAD-2, Milan, and UCSF. A new model combining biomarkers with tumor size at the time of transplant(S-LAD) demonstrated the highest predictive capability with c-statistics of 0.71 and 0.69 for recurrence and death. CONCLUSION BALAD and BALAD-2 are valid in transplant HCC patients, but less predictive than the three biomarkers in combination or the three biomarkers in combination with maximal tumor diameter(S-LAD). | Nicha Wongjarupong Gabriela M Negron-Ocasio Roongruedee Chaiteerakij Benyam D Addissie Essa A Mohamed Kristin C Mara William S Harmsen J Paul Theobald Brian E Peters Joseph G Balsanek Melissa M Ward Nasra H Giama Sudhakar K Venkatesh Denise M Harnois Michael R Charlton Hiroyuki Yamada Alicia Algeciras-Schimnich Melissa R Snyder Terry M Therneau Lewis R Roberts | 2018 | World Journal of Gastroenterology2018，24，12： | 5 |
| 5 | Setup, deposition, and sedimentary characteristics of two storm overwash deposits, Abrahams Bosom Beach, Southeastern Australia显示文摘 | Adam D S Brian G J | 2008 | Journal of Coastal Research2008，，： | 1 |
| 6 | 显示文摘 | Trewyn Brian G Whitman Chad M Lin Victor S Y | 2004 | Nanoletters2004，11，4： | 1 |
| 7 | Near infrared spectroscopy in the forest products industry显示文摘 | Chi-Leung S O Brian KV Leslie H G | 2004 | Forest Products Journal2004，54，3： | 1 |
| 8 | Tacrolimus for the treatment of fistulas in patients with crohn’s disease: a randomized, placebo-controlled trial显示文摘 | William J Sandborn Daniel H Present Kim L Isaacs Douglas C Wolf Eugene Greenberg Stephen B Hanauer Brian G Feagan Lloyd Mayer Therese Johnson Joseph Galanko Christopher Martin Robert S Sandler | 2003 | Gastroenterology2003，，2： | 1 |
| 9 | Constraints on the acquisition of remanent magnetization in fine-grained sediments imposed by redeposition experiments显示文摘 | BRIAN C S JEAN P V MAXIME L G | 2006 | Earth and Planetary Science Letters2006，245，： | 1 |
| 10 | Substrate-assisted catalysis in sialic acid aldolase 显示文摘 | Brian J S Michael C L Joao A R G B | 1999 | J Org Chem1999，64，： | 1 |
| 11 | Transoral Incisionless Fundoplication: 2-year Results from the Prospective Multicenter U.S. Study显示文摘 | Bell Reginald C W Barnes William E Carter Bart J Sewell Robert W Mavrelis Peter G Ihde Glenn M Hoddinott Kevin M Fox Mark A Freeman Katherine D Gunsberger Tanja Hausmann Mark G Dargis David Gill Brian DaCosta Wilson Erik Trad Karim S | 2014 | The American Surgeon2014，，11： | 1 |
| 12 | A metal-free organic-inorganic aqueous flow battery显示文摘 | Huskinson Brian Marshak Michael P Suh Changwon Er Süleyman Gerhardt Michael R Galvin Cooper J Chen Xudong Aspuru-Guzik Alán Gordon Roy G Aziz Michael J | 2014 | Nature2014，505，7482： | 1 |
| 13 | Molecular characterization and sex- specific tissue expression of prolactin, somatolactin andinsulin-like growth factor-I in yellow perch(Percaflavescens) 显示文摘 | SCOTT G L BRIAN S S | 2007 | Comparative Biochemistry and Physiology2007，，147： | 1 |
| 14 | A two-phase study evaluating the relationship between Thimerosal-containing vaccine administration and the risk for an autism spectrum disorder diagnosis in the United States显示文摘Background:Autism spectrum disorder(ASD)is defined by standardized criteria of qualitative impairments in social interaction,qualitative impairments in communication,and restricted and stereotyped patterns of behavior,interests,and activities.A significant number of children diagnosed with ASD suffer a loss of previously-acquired skills,which is suggestive of neurodegeneration or a type of progressive encephalopathy with an etiological pathogenic basis occurring after birth.To date,the etiology of ASD remains under debate,however,many studies suggest toxicity,especially from mercury(Hg),in individuals diagnosed with an ASD.The present study evaluated concerns about the toxic effects of organic-Hg exposure from Thimerosal(49.55%Hg by weight)in childhood vaccines by conducting a two-phased(hypothesis generating/hypothesis testing)study with documented exposure to varying levels of Thimerosal from vaccinations.Methods:A hypothesis generating cohort study was undertaken to evaluate the relationship between exposure to organic-Hg from a Thimerosal-containing Diphtheria-Tetanus-acellular-Pertussis(DTaP)vaccine in comparison to a Thimerosal-free DTaP vaccine administered,from 1998 through 2000,for the risk of ASD as reported in the Vaccine Adverse Event Reporting System(VAERS)database(phase I).A hypothesis testing case–control study was undertaken to evaluate the relationship between organic-Hg exposure from Thimerosal-containing hepatitis B vaccines administered at specific intervals in the first six months of life among cases diagnosed with an ASD and controls born between 1991 through 1999 in the Vaccine Safety Datalink(VSD)database(phase II).Results:In phase I,it was observed that there was a significantly increased risk ratio for the incidence of ASD reported following the Thimerosal-containing DTaP vaccine in comparison to the Thimerosal-free DTaP vaccine.In phase II,it was observed that cases diagnosed with an ASD were significantly more likely than controls to receive increased organic-Hg from Thimerosal-containing hepatitis B vaccine administered within the first,second,and sixth month of life.Conclusions:Routine childhood vaccination is an important public health tool to reduce the morbidity and mortality associated with infectious diseases,but the present study provides new epidemiological evidence supporting an association between increasing organic-Hg exposure from Thimerosal-containing childhood vaccines and the subsequent risk of an ASD diagnosis. | David A Geier Brian S Hooker Janet K Kern Paul G King Lisa K Sykes Mark R Geier | 2013 | Translational Neurodegeneration2013，2，1： | 1 |
| 15 | Changes in the isotopic and chemical composition of ground water resulting from a recharge pulse from a sinking stream显示文摘 | Brian G Katz John S Catches | 1998 | Journal of Hydrology1998，，211： | 1 |
| 16 | Analysis of thermal and mechanical behavior of copper mould during thin slab casting显示文摘 | Joong K P Indira V S Brian G T | 2000 | Steelmaking Conference Proceedings2000，83，： | 1 |
| 17 | A multilocus sequence typing scheme for Streptococcus pneumoniae: identification of clones associ- ated with serious invasive disease 显示文摘 | Mark C E Brian G S | 1998 | Microhiol1998，144，： | 1 |
| 18 | Using linear algebra for intelligent information retrieval显示文摘 | Berry M W Dumais S T O' brian G W | 1995 | SIAM Review1995，37，4： | 1 |
| 19 | The role of bearing and scan mechanism life testing in flight qualification of the MODIS instrument显示文摘 | Steven G V Brian J D Kenneth W S | 2001 | Proceedings of the 35th Aerospace Mechanisms Symposium2001，5，： | 1 |
| 20 | Entrained-flow adsorption of mercury usiag activated carbon显示文摘 | Shannon D S Brian K G | 2001 | Air & Waste Manage2001，51，： | 1 |
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